Introduction: Presence of complement gene mutations is a risk factor for development of atypical hemolytic syndrome (aHUS). aHUS has high likelihood of recurrence in transplanted kidney and may result in graft loss and mortality. With limited treatment options in India, thrombotic microangiopathy (TMA) due aHUS recurrence needs to be diagnosed early and appropriate therapy needs to be initiated at the earliest. The objective of this study was to assess the outcomes of TMA due to aHUS recurrence in kidney transplant (KT) recipient.
Methods: The electronic database was reviewed to include the KT recipients who were diagnosed with TMA due to aHUS. aHUS was defined clinically as graft dysfunction, low hemoglobin, low platelet counts and increased lactate dehydrogenase. Outcomes in terms of graft function, graft loss, and mortality were assessed. Genetic mutations in complement factor H (CFH) and complement factors related (CFHR) genes were determined by multiplex ligation-dependent probe amplification (MLPA). Anti-factor H antibody (AFHAb)  levels were determined with ELISA.
Results: Between December 2020 and January 2024, 118 out of 255 chronic kidney patients patients screened for suspicion of aHUS had either raised AFHAb and/or CFH/CFHR mutations. Among them, 27 have undergone KT. Of these, 23 (85.2%) had CFH/CFHR mutations and 12 (44.4%) had raised AFHAb levels. Five patients (18.5%) developed aHUS recurrence post-transplant. In all the cases with aHUS recurrence, TMA was biopsy-proven. The average age of the cases was 35.6 years (range: 25 to 46 years) and all were males. MLPA testing was done pre-transplant in four (80.0%) cases and post-transplant in 1 patient (20%). CFHR 1/3 duplication and heterozygous deletion were present in four (80%) and one (20.0%) case, respectively. Pre-transplant evaluation of AFHAb was done in four (80.0%) cases. Only one had elevated AFHAb (229.6 AU/ml) at the time of KT. Based on pre-transplant evaluations, three cases were pre-emptively treated with PE and rituximab before KT. All received PE and two (40%) received rituximab for post-transplant aHUS recurrence. Graft loss occurred in one (20.0%) case. Four (80.0%) cases responded to therapy and have functioning graft with mean serum creatinine of 1.87 mg/dL. At latest follow-up (median: 94 weeks), all patients were alive. Post treatment, two (40.0%) patients had persistently raised AFHAb levels. Despite the raised AFHAb levels, no recurrence of TMA was noted in these patients during follow up.
Conclusion: aHUS recurrence after kidney transplant is dreadful. Presence of complement gene mutations in KT recipient poses unique challenges in India due to non-availability of complement inhibitors. PE along with rituximab may help in salvaging renal allograft after aHUS recurrence. Elevated AFHAb levels may trigger aHUS recurrence in early post-transplant period. Further studies are necessary to assess the role of rituximab in aHUS recurrence.